Synthesis and biological evaluation of a novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug for the treatment of hepatitis C virus infection

Ertong Li; Yafeng Wang; Wenquan Yu; Zhigang Lv; Youmei Peng; Bingjie Liu; Shiliang Li; Wenzhe Ho; Qingduan Wang; Honglin Li; Junbiao Chang

doi:10.1016/j.ejmech.2017.11.024

Synthesis and biological evaluation of a novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug for the treatment of hepatitis C virus infection

Ertong Li, Yafeng Wang, Wenquan Yu, Zhigang Lv, Youmei Peng, Bingjie Liu, Shiliang Li, Wenzhe Ho, Qingduan Wang, Honglin Li, Junbiao Chang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

A novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug (1) has been synthesized. This compound exhibits submicromolar-level antiviral activity in vitro against HCV genotypes 1b, 1a, 2a, and S282T replicons (EC₅₀ = 0.18–1.13 μM) with low cytotoxicity (CC₅₀ > 1000 μM). Administered orally, prodrug 1 is well tolerated at doses of up to 4 g/kg in mice, and produces a high level of the corresponding triphosphate in rat liver.

Original language	English
Pages (from-to)	107-113
Number of pages	7
Journal	European Journal of Medicinal Chemistry
Volume	143
DOIs	https://doi.org/10.1016/j.ejmech.2017.11.024
State	Published - 1 Jan 2018
Externally published	Yes

Keywords

2′-α-fluoro-2′-β-C-(fluoromethyl)uridine
Anti-HCV
Phosphoramidate prodrug
Triphosphate

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejmech.2017.11.024

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Li, E., Wang, Y., Yu, W., Lv, Z., Peng, Y., Liu, B., Li, S., Ho, W., Wang, Q., Li, H., & Chang, J. (2018). Synthesis and biological evaluation of a novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug for the treatment of hepatitis C virus infection. European Journal of Medicinal Chemistry, 143, 107-113. https://doi.org/10.1016/j.ejmech.2017.11.024

@article{e05e148701fa45cb812317ef34d9bf5d,

title = "Synthesis and biological evaluation of a novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug for the treatment of hepatitis C virus infection",

abstract = "A novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug (1) has been synthesized. This compound exhibits submicromolar-level antiviral activity in vitro against HCV genotypes 1b, 1a, 2a, and S282T replicons (EC50 = 0.18–1.13 μM) with low cytotoxicity (CC50 > 1000 μM). Administered orally, prodrug 1 is well tolerated at doses of up to 4 g/kg in mice, and produces a high level of the corresponding triphosphate in rat liver.",

keywords = "2′-α-fluoro-2′-β-C-(fluoromethyl)uridine, Anti-HCV, Phosphoramidate prodrug, Triphosphate",

author = "Ertong Li and Yafeng Wang and Wenquan Yu and Zhigang Lv and Youmei Peng and Bingjie Liu and Shiliang Li and Wenzhe Ho and Qingduan Wang and Honglin Li and Junbiao Chang",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Masson SAS",

year = "2018",

month = jan,

day = "1",

doi = "10.1016/j.ejmech.2017.11.024",

language = "英语",

volume = "143",

pages = "107--113",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

}

Li, E, Wang, Y, Yu, W, Lv, Z, Peng, Y, Liu, B, Li, S, Ho, W, Wang, Q, Li, H & Chang, J 2018, 'Synthesis and biological evaluation of a novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug for the treatment of hepatitis C virus infection', European Journal of Medicinal Chemistry, vol. 143, pp. 107-113. https://doi.org/10.1016/j.ejmech.2017.11.024

Synthesis and biological evaluation of a novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug for the treatment of hepatitis C virus infection. / Li, Ertong; Wang, Yafeng; Yu, Wenquan et al.
In: European Journal of Medicinal Chemistry, Vol. 143, 01.01.2018, p. 107-113.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Synthesis and biological evaluation of a novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug for the treatment of hepatitis C virus infection

AU - Li, Ertong

AU - Wang, Yafeng

AU - Yu, Wenquan

AU - Lv, Zhigang

AU - Peng, Youmei

AU - Liu, Bingjie

AU - Li, Shiliang

AU - Ho, Wenzhe

AU - Wang, Qingduan

AU - Li, Honglin

AU - Chang, Junbiao

PY - 2018/1/1

Y1 - 2018/1/1

N2 - A novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug (1) has been synthesized. This compound exhibits submicromolar-level antiviral activity in vitro against HCV genotypes 1b, 1a, 2a, and S282T replicons (EC50 = 0.18–1.13 μM) with low cytotoxicity (CC50 > 1000 μM). Administered orally, prodrug 1 is well tolerated at doses of up to 4 g/kg in mice, and produces a high level of the corresponding triphosphate in rat liver.

AB - A novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug (1) has been synthesized. This compound exhibits submicromolar-level antiviral activity in vitro against HCV genotypes 1b, 1a, 2a, and S282T replicons (EC50 = 0.18–1.13 μM) with low cytotoxicity (CC50 > 1000 μM). Administered orally, prodrug 1 is well tolerated at doses of up to 4 g/kg in mice, and produces a high level of the corresponding triphosphate in rat liver.

KW - 2′-α-fluoro-2′-β-C-(fluoromethyl)uridine

KW - Anti-HCV

KW - Phosphoramidate prodrug

KW - Triphosphate

UR - https://www.scopus.com/pages/publications/85034746337

U2 - 10.1016/j.ejmech.2017.11.024

DO - 10.1016/j.ejmech.2017.11.024

M3 - 文章

C2 - 29172078

AN - SCOPUS:85034746337

SN - 0223-5234

VL - 143

SP - 107

EP - 113

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Synthesis and biological evaluation of a novel β-D-2′-deoxy-2′-α-fluoro-2′-β-C-(fluoromethyl)uridine phosphoramidate prodrug for the treatment of hepatitis C virus infection

Abstract

Keywords

UN SDGs

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